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Updated: Jun 13, 2026

A Computational Modeling Approach to Investigate the Influence of Hyperthermia on the Tumor Microenvironment
Published on: December 1, 2023
Mathematical formulation and analysis of the nonlinear system reconstruction of the online image-guided adaptive
Kung-Shan Cheng1, Mark W Dewhirst, Paul F Stauffer
1Division of Radiation Oncology, Duke University Medical Center, Box 3295, Durham, North Carolina 27710, USA. acosine@yahoo.com
Purpose:
A nonlinear system reconstruction can theoretically provide timely system reconstruction when designing a real-time image-guided adaptive control for multisource heating for hyperthermia. This clinical need motivates an analysis of the essential mathematical characteristics and constraints of such an approach.
Methods:
The implicit function theorem (IFT), the Karush-Kuhn-Tucker (KKT) necessary condition of optimality, and the Tikhonov-Phillips regularization (TPR) were used to analyze and determine the requirements of the optimal system reconstruction. Two mutually exclusive generic approaches were analyzed to reconstruct the physical system: The traditional full reconstruction and the recently suggested partial reconstruction. Rigorous mathematical analysis based on IFT, KKT, and TPR was provided for all four possible nonlinear reconstructions: (1) Nonlinear noiseless full reconstruction, (2) nonlinear noisy full reconstruction, (3) nonlinear noiseless partial reconstruction, and (4) nonlinear noisy partial reconstruction, when a class of nonlinear formulations of system reconstruction is employed.
Results:
Effective numerical algorithms for solving each of the aforementioned four nonlinear reconstructions were introduced and formal derivations and analyses were provided. The analyses revealed the necessity of adding regularization when partial reconstruction is used. Regularization provides the theoretical support for one to uniquely reconstruct the optimal system. It also helps alleviate the negative influences of unavoidable measurement noise. Both theoretical analysis and numerical examples showed the importance of having a good initial guess for accomplishing nonlinear system reconstruction.
Conclusions:
Regularization is mandatory for partial reconstruction to make it well posed. The Tikhonov-Phillips regularized Gauss-Newton algorithm has nice theoretical performance for partial reconstruction of systems with and without noise. The Levenberg-Marquardt algorithm is a more robust algorithmic option compared to the Gauss-Newton algorithm for nonlinear full reconstruction. A severe limitation of nonlinear reconstruction is the time consuming calculations required for the derivatives of temperatures to unknowns. Developing a method of model reduction or implementing a parallel algorithm can resolve this. The results provided herein are applicable to hyperthermia with blood perfusion nonlinearly depending on temperature and in the presence of thermally significant blood vessels.
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